Duchenne Muscular DystrophyPhase 2NCT02167217
Historically Controlled Trial of Corticosteroids in Young Boys With Duchenne Muscular Dystrophy
A Phase 2 study testing Prednisolone in people with Duchenne Muscular Dystrophy, run by Washington University School of Medicine at 6 sites in United States.
Trial summary
While it has been known for many years that corticosteroid use benefits boys with Duchenne Muscular dystrophy (DMD), most clinicians do not consider treating until after age 3 or 4 years of age. Read more about this study
- Who is it for?
- Ages 1 month to 30 months, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- Prednisolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 6 sitesUnited States
- Study dates
- 17 Apr 2014to 22 Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 30 months
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Appropriate degree of weakness for age, creatine kinase greater than 20 times the upper limit of normal, and genetic mutation known to be causative for Duchenne muscular dystrophy .
- Appropriate degree of weakness for age, creatine kinase greater than 20 times the upper limit of normal and genetic or biopsy confirmation of Duchenne muscular dystrophy in a primary relative (e.g. brother or maternal uncle).
- De-identified, genetic studies will be reviewed by collaborator Kevin Flanigan, MD prior to enrollment of subjects.
- Age at entry: one month through 30 months.
Who cannot join
- Prior treatment with corticosteroids
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Laurie Children's Hospital Of Chicago
Chicago, Illinois, 60611-2605
Research Institute Center for Gene Therapy at Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas South Western Medical Center of Dallas
Dallas, Texas, 75390
Nemours Hospital
Orlando, Florida, 32827
University of California Davis
Sacramento, California, 95817
Washington University in Saint Louis
St Louis, Missouri, 63109
About this study
Official title: Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys With Duchenne Muscular Dystrophy
While it has been known for many years that corticosteroid use benefits boys with Duchenne Muscular dystrophy (DMD), most clinicians do not consider treating until after age 3 or 4 years of age. The primary reason for the delay is that daily corticosteroid use has many side effects including short stature, obesity, and osteoporosis. A recent randomized blinded study of weekend oral corticosteroid use over one year showed equal improvement in strength with fewer side effects, particularly as related to growth and cushingoid changes. The investigators will test the efficacy of oral weekend corticosteroid use in infants and young boys with DMD who are under age 30 months. The investigators have demonstrated that the Bayley-III Scales of Infant development shows that infants and young boys in this age group who are untreated decline in abilities when compared to their peers. Here, in this Phase 2 historically controlled trial, the investigators will use these two measures and treat boys at five Muscular Dystrophy Association-DMD centers
Read the detailed description
Objective. Determine if twice-weekly high dose oral prednisone improves gross motor development in infants and young boys with DMD. The investigators will perform a phase 2 historically controlled trial of oral twice-weekly prednisone (5mg/kg/dose on two consecutive days) in infants and young boys with DMD. Here the investigators propose to study the effect of this therapy in a multicenter trial of boys with DMD who are less than 30 months old at the baseline visit. Each boy will be followed for one year.
Aim 1. Determine if treatment improves gross motor function in infants with DMD over a 6-12-month period as measured by the Bayley-III. The Bayley-III infant score is the primary motor clinical endpoint of this therapeutic trial. Secondary outcomes include fine motor function, speech and language, and social function.
Aim 2. Determine if treatment improves the Adaptive Behavior Subtest of the Bayley-III (ABS) as scored by the infants' primary caregiver. In the study of untreated boys, the primary caregiver noted clear deficits, predominantly related to areas relevant to gross motor function. The ABS Aim 3. Determine if treatment improves performance on the North Star Ambulatory Assessment (NSAA) for those boys who are ambulatory.
Aim 4. Determine if treatment with weekly corticosteroids is tolerated and is safe in boys with DMD who are less than 30 months of age.
Objective 2. Determine if ultrasound of biceps and quadriceps using calibrated backscatter improves in infants and young boys with DMD who are treated with oral high dose weekly corticosteroids. Preliminary data of ultrasound imaging in infants and young boys with DMD demonstrate progressive structural damage as measured by calibrated backscatter. The ultrasound studies will be limited to the infants and boys who will enroll at the primary site (Washington University) where Dr. Craig Zaidman has the equipment and expertise to accomplish this aim.
Objective 3. Determine if caregiver burden changes with treatment of infants and young boys with DMD. Preliminary data from questionnaires suggests the caregiver burden for the primary caregiver of untreated infant and young boys with DMD is minimal. Assessment of this with in this trial will allow us to discern if this changes with a therapeutic trial.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- Prednisolone
- Keywords
- Duchenne Muscular Dystrophy, Corticosteroids, Infants, Young Children, Toddlers
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoloneDrug
Also called prednisolone (Morton Grove Pharm.) National Drug Code is 60432-212-08
Prednisolone (5mg per kg) will be taken on two consecutive days, Friday and Saturday mornings each week with breakfast
| Study group | Role | What they receive |
|---|---|---|
| Oral Prednisolone | Experimental | Oral Prednisolone 5mg/kg/ day on two consecutive days, Friday and Saturday with breakfast Receives: Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bayley III Gross Motor Scaled Score (Change From Baseline to 12 Month)
Bayley III Gross Motor Scaled Score measures motor development. This is normed for typically developing children and follow a bell shaped curve. The scale has mean of 10 +/-3 for children at all ages and is bell shaped. Therefore the two standard deviation range is 16 to 4 with higher values indicated better performance. Lower values have been shown to be common in boys with DMD and it this study the baseline average score was 4.2.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2014 (estimated)
- Study start17 Apr 2014
- Primary completion22 Feb 2017
- Study completion22 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Nationwide Children's Hospital, Northwestern University, University of Texas Southwestern Medical Center, University of California, Davis, Nemours Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Anne M Connolly, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02167217
- Sponsor's protocol ID
- 201308062
- Status last verified
- Dec 2018
- First submitted
- 3 Feb 2014
- Last updated
- 21 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Connolly AM, Florence JM, Cradock MM, Malkus EC, Schierbecker JR, Siener CA, Wulf CO, Anand P, Golumbek PT, Zaidman CM, Philip Miller J, Lowes LP, Alfano LN, Viollet-Callendret L, Flanigan KM, Mendell JR, McDonald CM, Goude E, Johnson L, Nicorici A, Karachunski PI, Day JW, Dalton JC, Farber JM, Buser KK, Darras BT, Kang PB, Riley SO, Shriber E, Parad R, Bushby K, Eagle M; MDA DMD Clinical Research Network. Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network. Neuromuscul Disord. 2013 Jul;23(7):529-39. doi: 10.1016/j.nmd.2013.04.005. Epub 2013 May 28.
PubMed 23726376Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002 Dec;12(10):917-25. doi: 10.1016/s0960-8966(02)00180-3.
PubMed 12467746Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, Kornberg AJ, Bertorini TE, Nevo Y, Lotze T, Pestronk A, Ryan MM, Monasterio E, Day JW, Zimmerman A, Arrieta A, Henricson E, Mayhew J, Florence J, Hu F, Connolly AM. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011 Aug 2;77(5):444-52. doi: 10.1212/WNL.0b013e318227b164. Epub 2011 Jul 13.
PubMed 21753160Connolly AM, Zaidman CM, Golumbek PT, Cradock MM, Flanigan KM, Kuntz NL, Finkel RS, McDonald CM, Iannaccone ST, Anand P, Siener CA, Florence JM, Lowes LP, Alfano LN, Johnson LB, Nicorici A, Nelson LL, Mendell JR; MDA DMD Clinical Research Network. Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy. Muscle Nerve. 2019 Jun;59(6):650-657. doi: 10.1002/mus.26441. Epub 2019 Feb 23.
PubMed 30706490
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Historically Controlled Trial of Corticosteroids in Young Boys With Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT02167217
- Acronym / sponsor ID
- 201308062
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Duchenne Muscular Dystrophy, Corticosteroids, Infants, Young Children, Toddlers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Nationwide Children's Hospital, Northwestern University, University of Texas Southwestern Medical Center, University of California, Davis, Nemours Children's Hospital
- Study start
- 17 Apr 2014 (actual)
- Primary completion
- 22 Feb 2017 (actual)
- Study completion
- 22 Mar 2017 (actual)
- First posted
- 19 Jun 2014 (estimated)
- Results
- Posted 18 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
While it has been known for many years that corticosteroid use benefits boys with Duchenne Muscular dystrophy (DMD), most clinicians do not consider treating until after age 3 or 4 years of age. The primary reason for the delay is that daily corticosteroid use has many side effects including short stature, obesity, and osteoporosis. A recent randomized blinded study of weekend oral corticosteroid use over one year showed equal improvement in strength with fewer side effects, particularly as related to growth and cushingoid changes. The investigators will test the efficacy of oral weekend corticosteroid use in infants and young boys with DMD who are under age 30 months. The investigators have demonstrated that the Bayley-III Scales of Infant development shows that infants and young boys in this age group who are untreated decline in abilities when compared to their peers. Here, in this Phase 2 historically controlled trial, the investigators will use these two measures and treat boys at five Muscular Dystrophy Association-DMD centers
Detailed description
Objective. Determine if twice-weekly high dose oral prednisone improves gross motor development in infants and young boys with DMD. The investigators will perform a phase 2 historically controlled trial of oral twice-weekly prednisone (5mg/kg/dose on two consecutive days) in infants and young boys with DMD. Here the investigators propose to study the effect of this therapy in a multicenter trial of boys with DMD who are less than 30 months old at the baseline visit. Each boy will be followed for one year.
Aim 1. Determine if treatment improves gross motor function in infants with DMD over a 6-12-month period as measured by the Bayley-III. The Bayley-III infant score is the primary motor clinical endpoint of this therapeutic trial. Secondary outcomes include fine motor function, speech and language, and social function.
Aim 2. Determine if treatment improves the Adaptive Behavior Subtest of the Bayley-III (ABS) as scored by the infants' primary caregiver. In the study of untreated boys, the primary caregiver noted clear deficits, predominantly related to areas relevant to gross motor function. The ABS Aim 3. Determine if treatment improves performance on the North Star Ambulatory Assessment (NSAA) for those boys who are ambulatory.
Aim 4. Determine if treatment with weekly corticosteroids is tolerated and is safe in boys with DMD who are less than 30 months of age.
Objective 2. Determine if ultrasound of biceps and quadriceps using calibrated backscatter improves in infants and young boys with DMD who are treated with oral high dose weekly corticosteroids. Preliminary data of ultrasound imaging in infants and young boys with DMD demonstrate progressive structural damage as measured by calibrated backscatter. The ultrasound studies will be limited to the infants and boys who will enroll at the primary site (Washington University) where Dr. Craig Zaidman has the equipment and expertise to accomplish this aim.
Objective 3. Determine if caregiver burden changes with treatment of infants and young boys with DMD. Preliminary data from questionnaires suggests the caregiver burden for the primary caregiver of untreated infant and young boys with DMD is minimal. Assessment of this with in this trial will allow us to discern if this changes with a therapeutic trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral Prednisolone | Experimental | Drug: PrednisoloneOral Prednisolone 5mg/kg/ day on two consecutive days, Friday and Saturday with breakfast |
Who may qualify
- Ages
- 1 month to 30 months
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Appropriate degree of weakness for age, creatine kinase greater than 20 times the upper limit of normal, and genetic mutation known to be causative for Duchenne muscular dystrophy .
- Appropriate degree of weakness for age, creatine kinase greater than 20 times the upper limit of normal and genetic or biopsy confirmation of Duchenne muscular dystrophy in a primary relative (e.g. brother or maternal uncle).
- De-identified, genetic studies will be reviewed by collaborator Kevin Flanigan, MD prior to enrollment of subjects.
- Age at entry: one month through 30 months.
Key exclusion criteria (1 listed)
- Prior treatment with corticosteroids
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrednisoloneAlso: prednisolone (Morton Grove Pharm.) National Drug Code is 60432-212-08Prednisolone (5mg per kg) will be taken on two consecutive days, Friday and Saturday mornings each week with breakfast | Drug | Oral Prednisolone |
Primary outcome
Bayley III Gross Motor Scaled Score (Change From Baseline to 12 Month)
Time frame: One year
Bayley III Gross Motor Scaled Score measures motor development. This is normed for typically developing children and follow a bell shaped curve. The scale has mean of 10 +/-3 for children at all ages and is bell shaped. Therefore the two standard deviation range is 16 to 4 with higher values indicated better performance. Lower values have been shown to be common in boys with DMD and it this study the baseline average score was 4.2.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23726376Connolly AM, Florence JM, Cradock MM, Malkus EC, Schierbecker JR, Siener CA, Wulf CO, Anand P, Golumbek PT, Zaidman CM, Philip Miller J, Lowes LP, Alfano LN, Viollet-Callendret L, Flanigan KM, Mendell JR, McDonald CM, Goude E, Johnson L, Nicorici A, Karachunski PI, Day JW, Dalton JC, Farber JM, Buser KK, Darras BT, Kang PB, Riley SO, Shriber E, Parad R, Bushby K, Eagle M; MDA DMD Clinical Research Network. Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network. Neuromuscul Disord. 2013 Jul;23(7):529-39. doi: 10.1016/j.nmd.2013.04.005. Epub 2013 May 28.
- Background: PubMed 12467746Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002 Dec;12(10):917-25. doi: 10.1016/s0960-8966(02)00180-3.
- Background: PubMed 21753160Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, Kornberg AJ, Bertorini TE, Nevo Y, Lotze T, Pestronk A, Ryan MM, Monasterio E, Day JW, Zimmerman A, Arrieta A, Henricson E, Mayhew J, Florence J, Hu F, Connolly AM. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011 Aug 2;77(5):444-52. doi: 10.1212/WNL.0b013e318227b164. Epub 2011 Jul 13.
- Derived from this study: PubMed 30706490Connolly AM, Zaidman CM, Golumbek PT, Cradock MM, Flanigan KM, Kuntz NL, Finkel RS, McDonald CM, Iannaccone ST, Anand P, Siener CA, Florence JM, Lowes LP, Alfano LN, Johnson LB, Nicorici A, Nelson LL, Mendell JR; MDA DMD Clinical Research Network. Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy. Muscle Nerve. 2019 Jun;59(6):650-657. doi: 10.1002/mus.26441. Epub 2019 Feb 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne M Connolly, MD principal investigator
Washington University School of Medicine
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prednisolone in people with Duchenne Muscular Dystrophy, run by Washington University School of Medicine at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bayley III Gross Motor Scaled Score (Change From Baseline to 12 Month) (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02167217, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2018.